rs12127589

chr1-196377936-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):c.1295-4688C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,840 control chromosomes in the GnomAD database, including 7,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (7005 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT2	NM_198503.5	c.1295-4688C>T		intron_variant		ENST00000294725.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT2	ENST00000294725.14	c.1295-4688C>T		intron_variant		1	NM_198503.5	P4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38954 AN: 151722 Hom.: 6980 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 39024 AN: 151840 Hom.: 7005 Cov.: 31 AF XY: 0.252 AC XY: 18673 AN XY: 74196

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.239

Alfa AF: 0.184 Hom.: 1495

Bravo AF: 0.270

Asia WGS AF: 0.138 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.18
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12127589; hg19: chr1-196347066;